Ai Yamamoto,
PhD

The overriding theme of our research is to examine the molecular mechanism of protein trafficking events that modulate neural function and neurodegeneration. Our studies have focused on two forms of protein trafficking, one that mediates elimination of abnormal cellular proteins and a second that modulates the function of normal cellular proteins. In the former case we seek to understand how protein cargoes implicated in degenerative diseases are selected for degradation by the macroautophagy pathway, and are currently exploring how selective and basal macroautophagic processes are regulated in the healthy and diseased brain. In the latter case, our goal is to identify how cholesterol rich membrane microdomains modulate the function of membrane proteins such as neurotransmitter transporters, and how this impacts neurotransmission.

The strategy underlying our work begins with fundamental biochemical and cell biological approaches to identify the key molecular regulators of a protein trafficking event. Our goal is to apply these findings to the developing and adult brain using mouse genetics, to determine if modulating our pathway of interest can modify disease states. Transitioning our cell-based findings into the correct environmental context is critical; the highly specialized nature of neural cell types can lead to unexpected adaptations of a cellular pathway. Moreover, the cellular needs of an embryonic brain may be quite distinct from an aging one. These hypotheses driven studies in mice then inform us how we can further interpret our cell based work in the context of neural function, and importantly, how we can apply our findings to disease.